ART for All

Year in Review |
December 30, 2015

ART for All

  1. Abigail Zuger, MD

World guidelines now agree that all HIV-positive patients should receive antiretroviral therapy after diagnosis.

  1. Abigail Zuger, MD

Ever since combination antiretroviral therapy (ART) transformed HIV into a chronic manageable disease, experts have debated the right time for patients to begin treatment. At first we delayed until patients got sick; then we waited for signs of serious immune depletion; then we began to prescribe medications for patients with even minimal immune depletion. The year 2015 saw the uniform recommendation that all HIV-positive people be treated immediately, regardless of duration of infection or immune status.

We have known for some time that patients who start treatment early often have better immunologic recovery than those who do not (NEJM JW Gen Med Jan 1 2015 and JAMA Intern Med 2015; 175:88). In 2015, we got invaluable clinical confirmation from the SMART study, in which researchers enrolled almost 5000 healthy HIV-positive patients from around the world, all with CD4 cell counts in the normal range (≥500 cells/mm3). Half started combination treatment immediately; half waited until CD4 cell count declined to ≤350 cells/mm3.

After 3 years, the overall rate of serious clinical events in the deferred-treatment group was almost twice that seen in the immediate-treatment group. The combined endpoint included AIDS-related events, other serious illnesses, and death from any cause: The difference was most pronounced for HIV-related conditions such as tuberculosis, lymphoma, and Kaposi sarcoma, for bacterial infections, and for cancers not related to AIDS (NEJM JW Gen Med Aug 15 2015 and N Engl J Med 2015; 373:795). Because of these dramatic results, the study was stopped early, and its results prompted a change in guidelines around the world.

Although the results of the START study are incontrovertible, they will lead to complicated challenges. Policymakers will have to figure out how to pay for expensive lifelong treatment for the world's HIV-positive population. Clinicians will face the always difficult task of convincing patients to adhere to medications when they feel just fine without them — a task made more complex than usual by the fact that, in HIV infection, drug resistance can result from suboptimal adherence to antiretroviral therapy.

Editor Disclosures at Time of Publication

  • Disclosures for Abigail Zuger, MD at time of publication Editorial boards Clinical Infectious Diseases; Open Forum Infectious Diseases

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